Hemorrhagic stroke or intracerebral hemorrhage (ICH) accounts for 10-15% of all stroke and is characterized by the bleeding and clotting in the brain caused by the rupture of blood vessels. Clinical treatments for ICH include craniotomy, a highly invasive surgery, and minimally invasive surgeries to drain the clot with catheter and thrombolytic drugs over several days. Due to the invasiveness, long treatment time, and the use of thrombolytic drugs, these treatments are associated with severe impairment of neurological function and poor outcome. MR-guided focused ultrasound (MRgFUS) is currently being investigated to improve ICH therapy. With MRgFUS applied outside the skull, the clot in the brain can be liquefied and aspirated out with a needle, providing a minimally invasive and faster treatment. Despite of the advancement, MRgFUS has the following three drawbacks: 1) It is cost prohibitive due to the long MRI hours required; 2) the treatment time is extensive for a large clot volume; and 3) It cannot treat tissue within 2 cm distance from the skullcap. Furthermore, all existing methods are not effective for large hematoma (>40mL). We propose to develop a new ultrasonic technology to treat ICH, termed histotripsy that has the potential to overcome each of the current limitations. Using ultrasound generated from outside the skullcap, histotripsy produces focal cavitation to liquefy the target clot. Compared to MRgFUS that needs >100s length pulses to generate cavitation, histotripsy can initiate cavitation using a single pulse of 14 s, and as a result is significantly faster and more efficient. Our preliminary data show that histotripsy liquefied in vitro clots of ~40mL volume through an excised human skullcap within 30 minutes, which is orders of magnitude faster than thrombolytic drugs and six fold faster than MRgFUS. It treated clots within 5 mm of the skullcap and is effective for clots larger than 40mL. The proposed aims address two major technical challenges to develop histotripsy for ICH therapy. In Aim 1, we will develop a new device and associated algorithm, with much reduced complexity compared to MRgFUS, to achieve transcranial histotripsy ICH therapy without MRI. In Aim 2, we will optimize the parameters to maximize the treatment speed and locations for transcranial histotripsy clot liquefaction. The proposed work will enable histotripsy to become a paradigm changing technology for ICH therapy and can be extended to other transcranial applications including ischemic stroke and brain tumor.